AndroBioSys, Inc. is dedicated to the development of human tissue-based in vivo tools capable of selecting better targeted agents for clinical trials by improved preclinical testing. AndroBioSys has developed the technology for reproducible implantation of primary xenografts of benign and malignant human prostate and kidney tissue. Xenografts have been established from over two hundred and fifty successive fresh surgical specimens and are characterized by maintenance of the tissue architecture of the tissue in the human donor, including the maintenance of a completely human vascular network and tissue microenvironment. The vascular endothelial cells of primary xenografts of benign and malignant human prostate tissue demonstrate active angiogenesis, express functional androgen receptor protein, and undergo a wave of apoptotic death upon androgen deprivation that precedes by several days the wave of apoptotic death of prostate epithelial or prostate cancer epithelial cells. In contrast, while the endothelial cells in primary xenografts of benign human kidney tissue or human renal cell carcinoma tissue are of human origin, the endothelial compartment demonstrates minimal angiogenic potential, does not express AR and does not undergo apoptotic death in response to androgen deprivation. Lastly, in support of the in vivo xenograft model, AndroBioSys has developed the expertise to establish primary cultures of human epithelial, stromal and endothelial cells from fresh surgical specimens of benign and malignant prostate and kidney tissue for prediction and/or verification of in vivo studies in matching primary xenografts. The goal of this application to the IMAT Program is to validate this in vitro/in vivo pre-clinical model system as a tool for analysis at the molecular level of: inter-individual differences in host biology; differences between the biology of individual cancers; and inter-individual differences in the host micro- environmental compartments. In addition, the Phase I program will evaluate the utility of this model for analysis of treatment modalities that target the human endothelial cell/vascular barrier, as a mechanism to modulate the bio-availability and response to therapeutic modalities, focusing on molecular endpoints measurable at the cellular, tissue and systemic (host serum) levels.
Public Health Relevance Statement: Project Narrative Preclinical models that more accurately reflect testing in human patients are urgently needed as the attrition rate for oncology drugs entering clinical trials approaches 95% and the cost to develop a drug that will reach the market currently is predicted to exceed $1.7 billion. AndroBioSys has developed a human tissue xenograft model that should more accurately reflect the microenvironment of human malignant and benign tissues. We are seeking funding through the IMAT program to develop this as a tool for evaluation of potential cancer drugs. AndroBioSys is poised to commercialize this system in a contract research service setting and believes that this will significantly reduce the cost of drug testing.
NIH Spending Category: Biotechnology; Cancer; Kidney Disease; Prostate Cancer; Urologic Diseases
Project Terms: Adenocarcinoma, Renal Cell; Androgen Receptor; Androgenic Agents; Androgenic Compounds; Androgens; Anti-Cancer Agents; Anti-Tumor Agents; Anti-Tumor Drugs; Antineoplastic Agents; Antineoplastic Drugs; Antineoplastics; Antiproliferative Agents; Antiproliferative Drugs; Apoptotic; Architecture; Assay; Basic Research; Basic Science; Benign; Bioassay; Bioavailability; Biologic Assays; Biologic Availability; Biological Assay; Biological Availability; Biological Models; Biology; Blood Serum; Blood Vessels; Body Tissues; Cancer Drug; Cancer of Prostate; Cancer, Oncology; Cancerous; Cancers; Carcinoma in Situ; Carcinoma, Hypernephroid; Carcinoma, Intraepithelial; Carcinoma, Preinvasive; Cells; Cessation of life; Chemotherapeutic Agents, Neoplastic Disease; Clinical Trials; Clinical Trials, Unspecified; DNA; Death; Deoxyribonucleic Acid; Development; Drugs; Endothelial Cells; Engineering / Architecture; Environment; Environmental Factor; Environmental Risk Factor; Epithelial; Epithelial Cells; Evaluation; Expression Profiling; Expression Signature; Funding; Gene Expression; Genital System, Male, Prostate; Goals; Grawitz Tumor; Harvest; Heterograft; Human; Human Prostate; Human Prostate Gland; Human, General; Hypernephroma; In Vitro; Individual; Individual Differences; Kidney; Maintenance; Maintenances; Malignant; Malignant - descriptor; Malignant Neoplasms; Malignant Tumor; Malignant Tumor of the Prostate; Malignant neoplasm of prostate; Malignant prostatic tumor; Man (Taxonomy); Man, Modern; Marketing; Math Models; Measurable; Medication; Modality; Model System; Modeling; Models, Biologic; Molecular; Molecular Analysis; Molecular Fingerprinting; Molecular Profiling; NCI; NCI Organization; National Cancer Institute; Nephroid Carcinoma; North Carolina; Operation; Operative Procedures; Operative Surgical Procedures; Outcome; Patients; Pattern; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Physiologic Availability; Pre-Clinical Model; Pre-Malignant; Preclinical Models; Preclinical Testing; Predisposition; Premalignant; Prevention; Programs (PT); Programs [Publication Type]; Prostate; Prostate CA; Prostate Cancer; Prostate Gland; Prostatic Cancer; Prostatic Gland; Proteins; Receptor Protein; Renal Adenocarcinoma; Renal Cell Cancer; Renal Cell Carcinoma; Renal Cell Carcinoma, Stage Unspecified; Research Contracts; Research Specimen; Role; Roswell Park Cancer Institute; Serum; Services; Specimen; Structure; Surgical; Surgical Interventions; Surgical Procedure; Susceptibility; System; System, LOINC Axis 4; Technology; Testing; Therapeutic; Therapeutic Androgen; Therapeutic Intervention; Tissues; Transplantation, Heterologous; Treatment Efficacy; Tumor-Specific Treatment Agents; Universities; Urinary System, Kidney; Variant; Variation; Vascular Endothelial Cell; Xenograft; Xenograft Model; Xenograft procedure; Xenotransplantation; adenocarcinoma of kidney; angiogenesis; anticancer agent; anticancer drug; base; bioavailability of drug; cancer risk; clinical investigation; cost; deprivation; drug detection; drug testing; drug/agent; environmental risk; gene product; human tissue; implantation; improved; in situ cancer; in vivo; innovate; innovation; innovative; intervention therapy; macromolecule; malignancy; mathematical model; mathematical modeling; molecuar profile; molecular signature; neoplasm/cancer; oncology; pre-clinical; precancerous; preclinical; programs; receptor; renal; response; social role; surgery; therapeutic efficacy; therapeutically effective; tool; tumor; vascular
